Major histocompatibility complex (MHC) is known as HLA (human leukocyte antigen) in human and is expressed in almost all cells and tissues. HLA mainly contains 6 gene loci antigens of A, B, C, DR, DQ and DP, each of which is constituted of complicated combinations of several dozen kinds of different types (allele) in tens of thousands of combinations. HLA is responsible for an important immune mechanism in the human body and the main role thereof is presentation of antigen to recognize self or non-self. When a person receives transplantation of a cell or tissue derived from other person (allogeneic transplantation), HLA is recognized as the most important antigen (foreign substance) by immunocompetent cells such as T cells and the like, whereby rejection is formed and the transplant is not engrafted.
In normal organ transplantation, particularly bone marrow transplantation, it is considered that all 6 gene loci of respective antigens A, B, C, DR, DQ and DP of HLA should in principle match; when they do not match, a risk of severe rejection response and bad prognosis after transplantation are foreseeable.
It is known that retinal pigment epithelial cell expresses or produces a molecule suppressing inflammatory cells that infiltrate intraocularly (Th1 cell, CD8 positive cell, macrophage, B cell and the like), and affords a suppressive signal on allogeneic autologous inflammatory cells (e.g., non-patent documents 1, 2). On the other hand, it is known that retinal pigment epithelial cell affords a promotive signal on regulatory T cells under similar conditions (non-patent documents 3, 4). On the other hand, retinal pigment epithelial cell is also known to suppress xenogeneic T cells (Th22 cell) (non-patent document 5), and it is known that retinal pigment epithelial cell itself has an immunosuppressive function, due to which the environment around retinal pigment epithelial cell tends to suppress immune reaction. Also, it is known that coculture of a human retinal pigment epithelial cell pre-treated with IFN-γ or macrophage with allogeneic T cells activates T cells since production of IL-2 and the like increases (non-patent document 6). IFN-γ is also known to play an important role in the expression of MHC class II molecule (non-patent document 7). However, an allogeneic transplantation strategy in consideration of HLA compatibility has not existed to date in the transplantation to retina disease patients by using a retinal pigment epithelial cell (hereinafter to be indicated as “RPE cell”).